title: Effects of metal binding on solubility and resistance of physiological prions depend on tissues and glycotypes.
abstract: Prion diseases entail the conversion of a normal host-encoded prion protein (PrP(C)) into an infectious isoform (PrP(Sc)). Various PrP(C) types differing in banding profiles and detergent solubility are present in different tissues, but only few PrP(Sc) types have been generated although PrP(C) acts as substrate. We hypothesize that distinct PrP(C) subtypes may be converted more efficiently to PrP(Sc) than others. One prerequisite for the analysis is the identification of the PrP(C) subtypes present in the protein complexes. Metal binding to PrP(C) is one of the most prominent features of the protein which induces increased proteolysis resistance and structural changes which might play an important role in the conversion process. Here we analyzed the metal-induced structural PrP(C) transformation of two different Triton X-100 soluble PrP(C) types derived from human platelets and brains by changes in protein solubility. We found that zinc and copper rendered approximately half of total PrP(C) and mainly un- and low-glycosylated PrP(C) to the Triton insoluble fraction. Our results indicate the presence of at least two distinct PrP(C) subtypes by metal interactions. The differentiation of high and low soluble metal bound PrP(C) offers precious information about PrP(C) protein composition and provides approaches for analyzing the transformation efficiency to PrP(Sc).
authors.affiliation: Institute for Hygiene, Westfälische Wilhelms-Universität and University Hospital Münster, Robert Koch-Strasse 41, 48149, Münster, Germany.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Kuczius
authors.forename: Reinhard
authors.initials: R
authors.lastname: Kelsch
mesh_terms: D003300:Copper / Q000737:chemistry / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D008670:Metals / Q000737:chemistry / Q000378:metabolism*; D017830:Octoxynol; D009928:Organ Specificity; D018620:PrPSc Proteins / Q000737:chemistry* / Q000378:metabolism; D017096:Prion Diseases / Q000378:metabolism* / Q000473:pathology; D011328:Prions / Q000737:chemistry / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism; D059748:Proteolysis; D012995:Solubility; D015032:Zinc / Q000737:chemistry / Q000378:metabolism
chemical_list: D008670:Metals; D018620:PrPSc Proteins; D011328:Prions; D020033:Protein Isoforms; D003300:Copper; D017830:Octoxynol; D015032:Zinc
keywords: COPPER; DETERGENT SOLUBILITY; METAL BINDING; PHYSIOLOGICAL PRION PROTEIN; ZINC